Direct observation of lattice symmetry breaking at the hidden-order transition in URu2Si2.

Since the 1985 discovery of the phase transition at THO=17.5 K in the heavy-fermion metal URu2Si2, neither symmetry change in the crystal structure nor large magnetic moment that can account for the entropy change has been observed, which makes this hidden order enigmatic. Recent high-field experiments have suggested electronic nematicity that breaks fourfold rotational symmetry, but direct evidence has been lacking for its ground state in the absence of magnetic field. Here we report on the observation of lattice symmetry breaking from the fourfold tetragonal to twofold orthorhombic structure by high-resolution synchrotron X-ray diffraction measurements at zero field, which pins down the space symmetry of the order. Small orthorhombic symmetry-breaking distortion sets in at THO with a jump, uncovering the weakly first-order nature of the hidden-order transition. This distortion is observed only in ultrapure samples, implying a highly unusual coupling nature between the electronic nematicity and underlying lattice.

A sharp peak of the zero-temperature penetration depth at optimal composition in BaFe2(As(1-x)P(x))2.

In a superconductor, the ratio of the carrier density, n, to its effective mass, m*, is a fundamental property directly reflecting the length scale of the superfluid flow, the London penetration depth, λ(L). In two-dimensional systems, this ratio n/m* (~1/λ(L)(2)) determines the effective Fermi temperature, T(F). We report a sharp peak in the x-dependence of λ(L) at zero temperature in clean samples of BaFe(2)(As(1)(-x)P(x))(2) at the optimum composition x = 0.30, where the superconducting transition temperature T(c) reaches a maximum of 30 kelvin. This structure may arise from quantum fluctuations associated with a quantum critical point. The ratio of T(c)/T(F) at x = 0.30 is enhanced, implying a possible crossover toward the Bose-Einstein condensate limit driven by quantum criticality.

[Postoperative right ventricular function after repair of tetralogy of Fallot with respect to the method of right ventricular outflow tract reconstruction].

We evaluated postoperative right ventricular function in the sixty-four consecutive patients with tetralogy of Fallot underwent total correction. The patients were divided to three groups according to the method of right ventricular outflow tract reconstruction: transannular patching (TA group; n = 31); right ventricular outflow patching with preservation of pulmonary valve ring (RV group; n = 12) and transatrial-transpulmonary approach without right ventriculotomy (no-RV group; n = 21). The early results of postoperative cardiac catheterization and echocardiography were compared among the three groups. Degree of pulmonary regurgitation was significantly low in the RV group and no-RV group compared with TA group (p < 0.005). Right ventricular ejection fraction was the highest in the no-RV group (p < 0.002). The repair without right ventriculotomy for tetralogy of Fallot can provide the best results with respect to postoperative right ventricular function.

Effects of prostaglandins on baroreflex during reperfusion of the ischaemic myocardium.

1. The present study was planned to: (i) determine whether the baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) was attenuated during reperfusion of short-term ischaemic myocardium; and (ii) study whether blockade of prostaglandin synthesis with indomethacin reversed the inhibitory baroreflex. 2. Arterial pressure was lowered with intravenous sodium nitroprusside before coronary occlusion and 3 min after release of a 5 min occlusion of the left circumflex coronary artery in anaesthetized rabbits. The protocol was repeated 20 min after indomethacin (5 mg/kg, i.v.) or indomethacin vehicle (50 mmol/L tris(hydroxymethyl)aminomethane buffer, pH 8.4) treatment. In addition, this study was performed in a group of vagotomized rabbits. 3. Before indomethacin treatment, the slope of the mean arterial pressure (MAP)-RSNA relationship decreased from -3.3+/-0.77 to -2.01+/-0.69% change in RSNA/mmHg (P < 0.05) during reperfusion of ischaemic myocardium in intact rabbits. The decrease in the slope was reversed by administration of indomethacin. However, the decrease in the slope was not reversed by indomethacin vehicle. Furthermore, the reduction in the slope of the MAP-RSNA relationship during reperfusion of ischaemic myocardium was abolished in vagotomized rabbits. However, there was no inhibition of the slope of the MAP-HR relationship during reperfusion of ischaemic myocardium in either intact or vagotomized rabbits. 4. In conclusion, our data suggest that prostaglandins released by ischaemic myocardium can attenuate the baroreflex-mediated response of RSNA to lowered arterial pressure via vagal afferents during reperfusion of short-term ischaemic myocardium.

Enhancement of delayed rectifier K+ current by P2-purinoceptor stimulation in guinea-pig atrial cells.

1. We studied the effects of P2-purinoceptor stimulation on the delayed rectifier K+ current (IK) in guinea-pig atrial myocytes using a whole-cell voltage-clamp technique. 2. External application of ATP increased IK, evoked by a 500 ms depolarizing pulse from a holding potential of -40 mV, under conditions in which the L-type Ca2+ channel was blocked; the effect was dose dependent with a half-maximal concentration (K1/2) of 0.95 microM. ATP (50 microM) produced a maximal increase of IK of about a factor of 2. 3. External ADP also enhanced IK in a dose-dependent manner with a K1/2 of 3.65 microM, whereas adenosine (100 microM) failed to evoke this response. Theophylline (500 microM), a blocker of the Pi-purinoceptor, did not antagonize the stimulating action of ATP on IK. These results indicate that IK was enhanced via P2-purinoceptors. 4. External ATP or ADP did not produce a significant change in the current kinetics of IK. 5. Pre-incubation of the atrial myocytes with pertussis toxin (PTX, 5 micrograms ml-1) did not affect the stimulating action of ATP on IK, indicating that PTX-sensitive G proteins did not mediate the ATP action. 6. The enhancement of IK by ATP developed slowly; the effects usually reached a maximum approximately 30-60 s after the application of ATP. This suggests the involvement of a diffusible cytosolic second messenger(s) in the response. ATP could further increase IK after maximal enhancement by isoprenaline (0.5-1.0 microM), suggesting that the intermediate steps were independent of cyclic AMP-dependent protein kinase (protein kinase A). 7. Potentiation of IK by ATP was not attenuated by either (i) pretreatment of the cells with 5 microM 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine dihydrochloride (H-7) or (ii) intracellular perfusion of 20 mM 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), suggesting that protein kinase C and intracellular Ca2+ did not mediate the response. 8. It is concluded that the activation of P2-purinoceptors increases IK through intracellular mechanisms independent of protein kinase A, protein kinase C or intracellular free Ca2+ in guinea-pig atrial myocytes.

Activation of the muscarinic K+ channel by P2-purinoceptors via pertussis toxin-sensitive G proteins in guinea-pig atrial cells.

1. Whole-cell voltage clamp and cell-attached patch-clamp techniques were applied to single atrial myocytes enzymatically dissociated from adult guinea-pig hearts. 2. In whole-cell clamp conditions, external applications, of ATP activated the muscarinic K+ (KACh) current, identified by its inward rectification, its reversal potential near the calculated K+ equilibrium potential (EK) and its relaxation properties during step changes of whole-cell membrane potential. Theophylline, an antagonist for Pi-purinoceptors, did not affect the action of ATP on the KACh current, indicating that the response was evoked through P2-purinoceptors. 3. The concentration-response relationship for ATP was well described by a Hill equation with a half-maximal concentration of 1.84 microM and a Hill coefficient of 0.94. ATP (100 microM) produced a maximal increase of the KACh current to 10.92 microA microF-1, which corresponds to 44.9 and 80.9% of the maximal increases evoked by ACh (10 microM) and adenosine (100 microM), respectively. 4. The activation of KACh current gradually declined to a steady level despite the continuous presence of ATP (desensitization). Recovery from the desensitization was relatively rapid with a half-time of approximately 1.5 min. 5. The activation of KACh current by ATP was completely abolished by pre-incubating myocytes with pertussis toxin (PTX, 5 micrograms ml-1), indicating that P2-purinoceptors are coupled to PTX-sensitive G proteins to activate the KACh channel. 6. In the cell-attached patch recording, ATP (5 microM) applied to the pipette solution enhanced the activity of a channel with single-channel conductance of 52.7 +/- 0.9 pS (mean +/- S.E.M., n = 10), reversal potential near EK and mean open time of 1.1 +/- 0.1 ms. These conductance and kinetic properties are identical to those of the KACh channel in the heart. In contrast, ATP applied to the bath solution did not significantly affect the basal activity of KACh channel openings. These observations suggest that the mechanism coupling the P2-purinoceptor to the activation of the KACh channel involves membrane-delimited component(s) rather than soluble second messenger(s). 7. These results strongly suggest a direct coupling of the P2-purinoceptor to the KACh channel through PTX-sensitive G proteins, analogous to the coupling mechanism of the muscarinic ACh receptor and Pi-purinoceptor to this channel.

A tumor-associated glycosylation change in the glucose transporter GLUT1 controlled by tumor suppressor function in human cell hybrids.

Studies of human cell hybrids have provided evidence that the tumorigenicity of a cervical carcinoma (HeLa) is under the control of a putative tumor suppressor on chromosome 11. Using these human cell hybrids, we found a tumor-associated glycosylation change in the glucose transporter GLUT1, which is an N-linked glycoprotein at the plasma membrane. The non-tumorigenic HeLa x fibroblast cell hybrid CGL1 and the normal diploid fibroblast WI38 expressed the 50-55 kDa GLUT1, whereas in a tumorigenic segregant hybrid, CGL4, as well as in parental HeLa cells, GLUT1 glycosylation was altered and its molecular mass was about 70 kDa. However, the altered GLUT1 glycosylation was not observed in SV40-transformed WI38 cells, suggesting a correlation between this glycosylation change and a putative tumor suppressor function. Further investigations using glycosidases, glycosylation inhibitors and lectin-affinity chromatography demonstrated that the tumor-associated glycosylation change in GLUT1 was mainly due to the increase in N-acetyl-lactosamine repeats in the N-linked oligosaccharides. In accordance with the altered glycosylation, affinity for 2-deoxyglucose in the tumorigenic CGL4 cells increased 2-fold, but there was little change in the Vmax. These results suggest there may be a functional role for the modulation by glycosylation of GLUT1 in the tumorigenic behavior of CGL4 and HeLa cells.

Effects of diltiazem and noradrenaline on extracellular potassium changes in the globally ischaemic rat heart.

OBJECTIVE: The aim was to investigate the effects of a calcium antagonist (diltiazem) and a catecholamine (noradrenaline) on extracellular potassium accumulation during global ischaemia. METHODS: Extracellular potassium concentration ([K+]e) was measured during 30 min global ischaemia in the isolated rat heart using a valinomycin potassium sensitive electrode. Contracture development during ischaemia was measured throughout with an intraventricular balloon inserted into the left ventricle and myocardial adenine nucleotides were measured in separate series of hearts. RESULTS: In control hearts, [K+]e showed a characteristic triphasic change during 30 min global ischaemia. This consisted of an early rising phase followed by a transient falling phase after the initial peak of [K+]e, and then a late rising phase. Diltiazem suppressed the rate of rise of [K+]e during early ischaemia, but extended the time course of the early [K+]e rise with the higher dose, abolishing the transient falling phase of [K+]e. During late ischaemia, the rise in [K+]e was attenuated by diltiazem. Noradrenaline also suppressed the early extracellular potassium accumulation, but in contrast to diltiazem, hastened the time course of the late [K+]e rise. CONCLUSIONS: Although diltiazem suppresses the early potassium loss during ischaemia as previously described, the drug also decreases the [K+]e fall by some as yet unknown mechanism, so that the [K+]e level becomes higher than control during the falling phase.

Arterial switch operation for transposition of the great arteries: surgical techniques to avoid complications.

From June 1984 to November 1990, 109 patients with transposition of the great arteries underwent arterial switch operation. There were 5 deaths, yielding a mortality rate of 4.6%. During this period, modifications of the surgical technique were devised to minimize intra- and postoperative problems, such as bleeding, kinking of the coronary arteries, aortic regurgitation and pulmonary stenosis. The surgical refinements that evolved include (1) a more distal division of the ascending aorta, (2) a punch technique for reimplantation of the coronary arteries in a medially rotated position, approximating the commissure, and superior to the upper border of the sinus of Valsalva, and (3) removal of left coronary ostia by incision down from the transected site to include a button of aortic wall, avoiding the free margin of the aorta and patch enlargement of the neopulmonary artery. Since instituting these refinements: (1) the time consumed for hemostasis after termination of the bypass considerably decreased from 111 +/- 59 to 87 +/- 51 minutes (p less than 0.05), (2) the incidence of kinking of the coronary arteries decreased from 29% (4/14) to 7% (6/88) (p less than 0.05), and (3) the occurrence of aortic insufficiency 1 year after correction was reduced from 36% (5/14) to 8% (5/66) (p less than 0.02). However, the occurrence of pulmonary stenosis with a pressure gradient greater than 30 mmHg did not decrease significantly despite aggressive modifications of surgical techniques, and its incidence in the most recent series of 32 patients was still a high 19%.

Analysis of determinants of ventricular fibrillation induced by reperfusion: dissociation between electrical instability and myocardial damage.

To assess the underlying mechanisms of ventricular fibrillation induced by myocardial reperfusion after cardioplegic arrest, 62 patients undergoing an open heart operation were divided into two groups based on the absence (group 1, n = 37) or the development (group 2, n = 25) of reperfusion-induced ventricular fibrillation. There was no close relationship between the incidence of reperfusion-induced ventricular fibrillation and aortic clamp time. On reperfusion, the time to onset of cardiac activity was similar in groups 1 (2.4 +/- 1.8 minutes) and 2 (1.9 +/- 1.1 minutes). At that time, there was no significant difference in values of arterial oxygen and bicarbonate contents, pH, or base excess between the two groups, but myocardial temperature was significantly higher in group 2 (25.6 degrees +/- 3.4 degrees versus 27.6 degrees +/- 2.4 degrees C; p less than 0.05). In addition, serum levels of sodium (123.9 +/- 4.2 versus 126.1 +/- 3.7 mmol/L; p less than 0.05) and calcium (0.80 +/- 0.07 versus 0.84 +/- 0.05 mmol/L; p less than 0.05) were significantly higher and serum potassium levels (3.98 +/- 0.58 versus 3.55 +/- 0.61 mmol/L; p less than 0.02) and the serum potassium to calcium ratio (4.94 +/- 0.90 versus 4.29 +/- 0.72; p less than 0.01) significantly lower in group 2. Postoperative serum levels of the myocardial-specific isoenzyme of creatine kinase and myoglobin were similar in both groups. By multivariate analysis, shorter ischemic time, higher myocardial temperature, higher serum sodium concentration, and lower serum potassium to calcium ratio were found to influence induction of reperfusion-induced ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of glibenclamide and nicorandil on cardiac function during ischemia and reperfusion in isolated perfused rat hearts.

We examined influences of a blocker (glibenclamide) and an opener (nicorandil) of the ATP-sensitive potassium (KATP) channel on extracellular K concentration [( K+]e), as well as the myocardial function and metabolites during global ischemia and reperfusion in Langendorff-perfused rat heart preparation. In control hearts, [K+]e began to rise 20 s after the onset of ischemia up to an initial peak (8.3 +/- 0.3 mM) at 2.5 +/- 0.7 min, then fell to 6.0 +/- 0.8 mM after 8.2 +/- 0.7 min, and then rose progressively to 14.6 +/- 0.8 mM at the end of 30 min of ischemia. Glibenclamide (50 microM) reduced the initial peak of [K+]e to 7.2 +/- 0.3 mM (P less than 0.01), and nicorandil (200 microM) increased it to 9.4 +/- 0.6 mM (P less than 0.01). There were no significant differences in [K+]e values among all groups at the end of ischemia. During ischemia, nicorandil decreased the time to mechanical arrest from 1.9 +/- 0.1 min to 1.5 +/- 0.1 min, whereas it was increased by glibenclamide to 2.7 +/- 0.4 min. In control hearts, the time to onset of ischemic contracture was 14.7 +/- 1.8 min. Nicorandil delayed onset of contracture and glibenclamide accelerated it. Thus we have confirmed that some part of the early increase in [K+]e during ischemia is attributable to K+ efflux through the KATP channel in our model, and opening of the KATP channel may contribute to a rapid reduction of the contractility of the ischemic myocardium that subsequently protects the myocardium against further ischemic injury.

Delayed time to peak serum myoglobin level as an indicator of cardiac dysfunction following open heart surgery.

Postoperative changes in serum myoglobin levels have been studied in 47 patients undergoing open heart surgery. The patients were retrospectively divided into two groups according to the time to peak myoglobin level during reperfusion. In 38 patients, myoglobin levels increased rapidly to a peak within 3 hours after reperfusion, after which it was cleared from the blood (group 1). Contrarily, a rise in myoglobin levels was persistent for 24 hours and its time to peak was greater than 3 hours after reperfusion in nine patients (group 2). There were no differences in preoperative and early reperfusion (within 1 hour of reperfusion) values of myoglobin between the two groups. At 3, 6, and 12 hours of reperfusion, myoglobin levels were significantly greater in group 2: 448 +/- 196 vs 1,149 +/- 900 ng/ml, 359 +/- 172 vs 2,653 +/- 3,179 ng/ml, 184 +/- 95 vs 1,896 +/- 1,387 ng/ml, respectively, p less than 0.0001 in each. The maximum activities of both myoglobin and CK-MB were significantly higher in group 2 (myoglobin-max: 771 +/- 257 vs 3,221 +/- 3,024 ng/ml, p less than 0.0001; CK-MBmax: 107 +/- 60 vs 227 +/- 219 IU/L, p less than 0.005). Five of nine patients in group 2 required post-operative assistance with intra-aortic balloon pumping (p less than 0.0005 compared with one of 38 in group 1) and perioperative myocardial infarction developed in three patients (33.3 percent) in this group (p less than 0.005 compared with 0 percent in group 1). Thus, patients with a delayed peak of serum myoglobin level exhibited detrimental cardiac failure postoperatively. These findings suggest that myocardial injury accelerated by reperfusion following ischemia might progress in these patients.

[A case report of total anomalous pulmonary venous drainage corrected with Vargas' method].

A 50-day-old infant with Darling's type Ib of total anomalous pulmonary venous drainage (TAPVD) was operated on with the Vargas' method. Pulmonary veins drained separately into the right superior vena cava (SVC). A J-shaped right atriotomy was performed according to the Vargas' method. The posterior flap was sutured to the anterior border of a previously enlarged atrial septal defect, directing the pulmonary blood flow toward the left atrium. The right SVC was divided just above the site of drainage of pulmonary veins, the proximal end of the right SVC was closed, and the anastomosis between the distal end of the right SVC and the previously opened right atrial appendage was performed. However, pulmonary hypertension remained because of the restrictive orifices of pulmonary venous drainage into SVC, and then side-to-side anastomoses between pulmonary veins and left atrium had to be added. Eight months after the operation pulmonary hypertension progressed markedly, because the orifices of the anastomoses became severely stenotic. Re-operation was performed to create a large anastomosis between pulmonary veins and left atrium. The indication and the long-term prognosis of the Vargas' method were discussed.

[Effects of oral administration of UFT in unresectable gastric cancer with liver metastasis].

A 62-year-old male was admitted because of upper abdominal mass. Exploratory laparotomy revealed unresectable gastric cancer, liver metastases and swelling of regional lymph nodes. Histological examination showed papillotubular adenocarcinoma. After 6 months' postoperative administration of UFT at a daily dose of 600 mg, X-ray and endoscopic examination revealed remarkable improvement of the gastric cancer. Computed tomography and ultrasonography showed disappearance of the mass in the liver and a remarkable decrease in the size of paraaortic lymph nodes. The cancer marker, serum CEA also decreased from 5.2 ng/ml to 2.1 ng/ml. At present, the abdominal mass is not palpable and the patient is asymptomatic except for pigmentation and being followed up in the outpatient department. This case suggests the possibility that UFT may be effective for advanced gastric cancer with liver metastases.